Homozygous, Intragenic Tandem Duplication of SFTPB Causes Neonatal Respiratory Failure

Wambach et al discuss how homozygous intragenic tandem duplication of SFTPB causes neonatal respiratory failure. This study reports a case of neonatal respiratory failure caused by a homozygous intragenic tandem duplication of the SFTPB gene. The duplication was identified in a term infant male proband and his female full siblings who underwent lung transplantation or died due to progressive respiratory failure. Functional studies on lung tissue from the proband confirmed the pathogenicity of the duplication. The duplication was flanked by Alu elements, which are repetitive DNA sequences that can mediate nonallelic chromosomal rearrangements. This is the first report of a homozygous pathogenic partial gene copy number gain in SFTPB. The study highlights the importance of genetic testing in infants with persistent respiratory failure and the potential of long-read sequencing to detect structural variants that may be missed by short-read sequencing.